1. Field of the Invention
There is a wide variety of situations where one is interested in the binding of a ligand and its receptor, particularly haptens and antigens with their respective antibodies. In many assays involving ligand-receptor binding, the concentrations of interest are extremely low and in view of the thermal lability of the reactants, elevated temperatures are precluded. In many instances, mechanical agitation, such as vortexing or rapid stirring, is precluded.
The problem is exacerbated when one of the members of the ligand-receptor pair is bound to a solid support. In effect, the diffusion rate for such a member is zero and one must depend on the diffusion of the other member of the pair for the combining reaction. Furthermore, with one of the members being a large protein, such as an antibody, the rate of diffusion is quite slow. Thus, in situations involving low rates of diffusion and low concentrations of one or both of the binding pair, it becomes important to find techniques to enhance the rate at which the two members of the binding pair react to form a complex.
2. Description of the Prior Art
See Berezin, et al., Mechanosensitive and Sound-Sensitive Enzymatic Systems as Chemical Amplifiers of Weak Signals, in "Immobilized Enzymes and Proteins," ed. Thomas Ming Swi Chang, Plenum Press, New York, Vol. 2, 1979, pps. 237-251 and Methods and Phenomena, Vol. 3, Pt. 2; "Ultra Sound; Its Applications in Medicine and Biology," Fry, Francis J., Ed., Elsevier, Amsterdam, Netherlands, 1978, 210. Stein, et al., J. Inorg. Biochem., (1982) 16:71-7 describe the effect of sample preparation on analysis of superoxide dismutase activity and isoenzymes, where the effect of sonication is reported. Ishimori, et al., J. Mol. Catal., (1981), 12:253-9 describe the acceleration of immobilized .alpha.-chymotrypsin activity with ultrasonic irradiation. Kashkooli, et al., J. Acoust. Soc. Am., (1980) 67:1798-1801 describe the effects of ultrasound on catalase and malate dehydrogenase. Fischer, J. Ger. Appl No. 144,558 describes increasing the activity of immobilized enzymes by ultrasonic treatment of the organic carrier. Schmidt, P. (Ger. Appl. No. 150,628) describes the reactivation of immobilized enzymes by ultrasonic treatment. See also Chemical Abstracts 89:2794Y; 96:179390j; 96:138563Z; 95:146154m; 93:64760A; 92:142400d; 96:118157s. See also an article in High Technology, entitled "Perspectives," March, 1983.